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Diabetologia. 2013 Apr;56(4):901-10. doi: 10.1007/s00125-012-2814-8. Epub 2013 Jan 12.

Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice.

Author information

1
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2200 Pierce Avenue, 560 RRB, Nashville, TN 37232-6602, USA.

Abstract

AIMS/HYPOTHESIS:

Obesity is associated with aldosterone excess, hypertension and the metabolic syndrome, but the relative contribution of aldosterone to obesity-related complications is debated. We previously demonstrated that aldosterone impairs insulin secretion, and that genetic aldosterone deficiency increases glucose-stimulated insulin secretion in vivo. We hypothesised that elimination of endogenous aldosterone would prevent obesity-induced insulin resistance and hyperglycaemia.

METHODS:

Wild-type and aldosterone synthase-deficient (As (-/-)) mice were fed a high-fat (HF) or normal chow diet for 12 weeks. We assessed insulin sensitivity and insulin secretion using clamp methodology and circulating plasma adipokines, and examined adipose tissue via histology.

RESULTS:

HF diet induced weight gain similarly in the two groups, but As (-/-) mice were protected from blood glucose elevation. HF diet impaired insulin sensitivity similarly in As (-/-) and wild-type mice, assessed by hyperinsulinaemic-euglycaemic clamps. Fasting and glucose-stimulated insulin were higher in HF-fed As (-/-) mice than in wild-type controls. Although there was no difference in insulin sensitivity during HF feeding in As (-/-) mice compared with wild-type controls, fat mass, adipocyte size and adiponectin increased, while adipose macrophage infiltration decreased. HF feeding significantly increased hepatic steatosis and triacylglycerol content in wild-type mice, which was attenuated in aldosterone-deficient mice.

CONCLUSIONS/INTERPRETATION:

These studies demonstrate that obesity induces insulin resistance independently of aldosterone and adipose tissue inflammation, and suggest a novel role for aldosterone in promoting obesity-induced beta cell dysfunction, hepatic steatosis and adipose tissue inflammation.

PMID:
23314847
PMCID:
PMC3593801
DOI:
10.1007/s00125-012-2814-8
[Indexed for MEDLINE]
Free PMC Article
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